Interventions for preventing critical illness polyneuropathy and critical illness myopathy
Abstract
Background
Critical illness polyneuro‐and/or myopathy (CIP/CIM) is an important and frequent complication in the intensive care unit (ICU), causing delayed weaning from mechanical ventilation. It may increase ICU stay and mortality.
Objectives
To examine the ability of any intervention to prevent the occurrence of CIP/CIM.
Search methods
We searched the Cochrane Neuromuscular Disease Group Trials Register (October 2007), MEDLINE (January 1950 to April 2008), EMBASE (January 1980 to October 2007), checked bibliographies and contacted trial authors and experts in the field.
Selection criteria
All randomised controlled trials (RCTs), examining the effect of any intervention on the incidence of CIP/CIM in adult medical or surgical ICU patients. The primary outcome measure was the incidence of CIP/CIM after at least seven days in ICU, based on electrophysiological or clinical examination.
Data collection and analysis
Two authors independently extracted the data.
Main results
Three out of nine identified trials, provided data on our primary outcome measure. Two trials examined the effects of intensive insulin therapy versus conventional insulin therapy. Eight hundred and twenty‐five out of 2748 patients randomised, were included in the analysis. The incidence of CIP/CIM was significantly reduced with intensive insulin therapy in the population screened for CIP/CIM (relative risk (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.78) and in the total population randomised (RR 0.60, 95% CI 0.49 to 0.74). Duration of mechanical ventilation, duration of ICU stay and 180‐day mortality but not 30‐day mortality, were significantly reduced with intensive insulin therapy, in both the total and the screened population. Intensive insulin therapy significantly increased hypoglycaemic events and recurrent hypoglycaemia. Death within 24 hours of the hypoglycaemic event was not different between groups. The third trial examined the effects of corticosteroids versus placebo in 180 patients with prolonged acute respiratory distress syndrome. No significant effect of corticosteroids on CIP/CIM was found (RR 1.09, 95% CI 0.53 to 2.26). No effect on 180‐day mortality, new serious infections and glycaemia at day seven was found. A trend towards fewer episodes of pneumonia and reduction of new events of shock was shown.
Authors' conclusions
Substantial evidence shows that intensive insulin therapy reduces the incidence of CIP/CIM, the duration of mechanical ventilation, duration of ICU stay and 180‐day mortality. There was a significant associated increase in hypoglycaemia. Further research needs to identify the clinical impact of this and strategies need to be developed to reduce the risk of hypoglycaemia. Limited evidence shows no significant effect of corticosteroids on the incidence of CIP/CIM, or on any of the other secondary outcome measures, except for a significant reduction of new episodes of shock. Strict diagnostic criteria for the purpose of research should be defined. Other interventions should be investigated in randomised controlled trials.
PICOs
Plain language summary
Interventions to reduce neuromuscular complications acquired during the acute phase of critical illness
Neuromuscular problems are frequent complications in patients with severe disease that require admission to the intensive care unit (ICU). Weakness of limbs and respiratory muscles is most frequently due to critical illness polyneuro‐and/or myopathy (CIP/CIM). As a consequence, patients face a delay in weaning from ventilatory support and rehabilitation. Recovery of strength often occurs within weeks to months but can be incomplete or not occur at all. CIP/CIM is associated with increased ICU stay and mortality rates. Prevention and treatment of CIP/CIM is therefore of great importance.
We searched for and analysed all randomised controlled trials that examined the effects of any treatment intervention on the incidence of CIP/CIM in adult patients admitted to an ICU. We ultimately found three trials that focused on two different interventions.
Two trials with 825 participants examined the effect of intensive insulin therapy, aiming to maintain blood glucose levels within the normal range (80 to 110 mg/dl), versus conventional insulin therapy, aiming to avoid hyperglycaemia (high blood sugar > 215 mg/dl), on the incidence of CIP/CIM in patients staying in ICU for at least one week. Pooling the results of both trials showed that intensive insulin therapy reduces the incidence of CIP/CIM, the duration of mechanical ventilation, the duration of ICU stay and mortality at 180 days. No significant effect on mortality at 30 days was noted. Intensive insulin therapy was associated with a significant increase in hypoglycaemia (low blood sugar), and recurrent hypoglycaemic events. Although no increase in mortality within 24 hours of hypoglycaemia was noted, hypoglycaemia remains an issue of concern when implementing intensive insulin therapy in critically ill patients, as it may cause neurological complications. In both trials, no clinical measurement of weakness of the limbs was reported, nor data on physical rehabilitation. Data were derived from subgroup analysis, which may also limit the conclusions.
The third trial compared corticosteroid therapy versus placebo in 180 patients with persisting acute respiratory distress syndrome. Results showed no evidence of an effect of corticosteroids on the incidence of CIP/CIM, no effect on mortality at 180 days, on new serious infections, on glucose levels on day 7 and a trend towards less episodes of suspected or probable pneumonia. The number of new events of shock was reduced. In this trial, only 92 of the 180 patients were prospectively evaluated for CIP/CIM.
